The overall goal of this project is to develop bovine and human Lactoferrins as an adjuvant to augment antibody and cell mediated immunity. We will specifically address the efficacy of Lactoferrin as an adjuvant to augment efficacy of BCG vaccination to subsequent challenge with virulent Mycobacterium tuberculosis. Improved nontoxic adjuvants, especially adjuvants capable of inducing (CM are needed for research use and for development of human and veterinary vaccines. The only adjuvant licensed for human use, alum, effectively enhances antibody formation, but is seldom effective for inducing CMI. Other adjuvants such as saponin and Complete Freund's that do induce CMI are much too toxic for use in humans and are being progressively restricted in animals. Lactoferrin is different from microbial derivative adjuvants, and from cytokines and growth factors; it is an effector molecule that directly participates in host defenses. Available evidence indicatesLactoferrin participates in the induction of immune responses, especially CMI. Preliminary studies demonstrate that lactoferrin as an adjuvant enhances delayed type hypersensitivity (DTH) in mice in a dose dependent fashion and has low toxicity. Furthermore, it induces IL-12, IL-15 and TNF-a production by macrophages thereby generating a local environment likely to push immune responses towards development of CMI.